The purpose of the proposed studies is to examine the role of somatomedin in normal skeletal development and in skeletal pathology. We are currently pursuing evidence that physeal chondrocytes, the cells responsible for skeletal growth, possess specific receptors for Multiplication Stimulating Activity (MSA) and are investigating the relationship between this receptor and that previously characterized for somatomedin-C (Sm-C). Additional studies have been initiated to evaluate somatomedin interaction with physeal chondrocytes at different stages in their maturation through the endochondral sequence. A possible role for somatomedin in osteoarthritis will be assessed through comparative studies of somatomedin interaction with articular chondrocytes from normal and osteoarthritic cartilage. Finally, because skeletal growth appears to be dependent upon somatomedin, we are intitiating studies to compare somatomedin interaction with physeal chondrocytes and the characteristics of the Sm receptor in disorders of skeletal growth (e.g., achondroplasia).